Valdoxan(reg): A New Approach to The Treatment of Depression

First Melatonergic Agonist Antidepressant Shows Efficacy and Tolerability Benefits Over Existing Therapies -


Valdoxan(reg) (agomelatine), the first melatonergic (MT1 and MT2 receptor) agonist antidepressant, is an innovation in the
treatment of depression with several advantages over existing treatments according to data presented during the 13th Congress
of the Association of European Psychiatrists. Besides being an effective antidepressant, Valdoxan has shown particular
advantages in improving the often disrupted sleep patterns of depressed patients, without affecting daytime vigilance.



"Agomelatine is an interesting and potentially very valuable antidepressant that is effective in both moderate and severe
depression", says Professor Stuart Montgomery from the Imperial College School of Medicine in London. "The new agent has a
unique mode of action, improves sleep without affecting daytime alertness and its efficacy is not compromised by sexual side
effects, tolerability problems or discontinuation symptoms."


Antidepressant efficacy


The antidepressant efficacy of Valdoxan has been shown at a standard dose of 25 mg, once daily in the evening, in a
dose-ranging study performed in major depressive disorder (MDD)1. In this multicentre, placebo-controlled, dose-ranging
study over eight weeks, Valdoxan was shown to be an effective antidepressant at a dose of 25 mg once daily, by reducing the
initial HAMD score to a similar extent to that of the SSRI paroxetine. Further studies versus placebo and comparators have
confirmed the efficacy of Valdoxan in adults of all ages, including the severely depressed and elderly depressed. Results
from another clinical trial presented here in Munich show that Valdoxan has a similar efficacy to the SNRI venlafaxine.



Improvements of disturbed wake-sleep cycles


"The ability to relieve sleep problems without being sedative is a key advantage for depressed patients who frequently suffer
from sleep disturbances associated with their depression", points out Christian Guilleminault, MD, from Stanford University
Sleep Disorders Clinic, California.


Due to its unique pharmacological profile, Valdoxan is the only antidepressant to have a specific action on circadian
rhythms, which are often imbalanced in depressed patients. By improving disturbed wake-sleep patterns, according to Dr
Guilleminault, Valdoxan is able to relieve sleep complaints of depressed patients with a favourable impact on daytime
vigilance.


Tolerability profile


Data presented by Professor Montgomery shows that Valdoxan provides antidepressant efficacy, but lacks typical antidepressant
side effects. The new agent does not appear to impair sexual function. A study comparing Valdoxan with venlafaxine showed
comparable antidepressant efficacy of both treatments, but significantly less sexual dysfunction of Valdoxan compared to the
SNRI. In addition, a placebo-controlled, double-blind study comparing Valdoxan with paroxetine showed that, after one week
of treatment discontinuation, no signs of discontinuation symptoms* were seen in the agomelatine group compared to
significant discontinuation symptoms in the paroxetine group.2


Valdoxan was discovered and developed by Servier. The drug is currently in Phase III and a registration dossier for an
indication in MDD was recently submitted to the European Regulatory Agency (EMEA).


Discontinuation symptoms occur when treatment with certain antidepressants (mainly SSRIs and SNRIs) is stopped. They can
include nausea, headache, dizziness, sleep disturbances, anxiety and irritability.


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For further information, please contact:

Moira Gitsham, Tonic Life Communications (+33 5 46 00 08 20, moira.gitshamtoniclc)

or

Matthew Kent, Tonic Life Communications (+44 207 798 9900, matthew.kenttoniclc)

References

1 L???o H, Hale A, D'haenen H. Int Clin Psychopharmacol. 2002; 17:239-247

2 Montgomery SA, Kennedy SH, Burrows GD, Lejoyeux M, Hindmarch I. Int Clin Psychopharmacol. 2004; 19 :271-280


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